200 research outputs found
Genomic Risk Factors Driving Immune-Mediated Delayed Drug Hypersensitivity Reactions
Adverse drug reactions (ADRs) remain associated with significant mortality. Delayed hypersensitivity reactions (DHRs) that occur greater than 6 h following drug administration are T-cell mediated with many severe DHRs now associated with human leukocyte antigen (HLA) risk alleles, opening pathways for clinical prediction and prevention. However, incomplete negative predictive value (NPV), low positive predictive value (PPV), and a large number needed to test (NNT) to prevent one case have practically prevented large-scale and cost-effective screening implementation. Additional factors outside of HLA contributing to risk of severe T-cell-mediated DHRs include variation in drug metabolism, T-cell receptor (TCR) specificity, and, most recently, HLA-presented immunopeptidome-processing efficiencies via endoplasmic reticulum aminopeptidase (ERAP). Active research continues toward identification of other highly polymorphic factors likely to impose risk. These include those previously associated with T-cell-mediated HLA-associated infectious or auto-immune disease such as Killer cell immunoglobulin-like receptors (KIR), epistatically linked with HLA class I to regulate NK- and T-cell-mediated cytotoxic degranulation, and co-inhibitory signaling pathways for which therapeutic blockade in cancer immunotherapy is now associated with an increased incidence of DHRs. As such, the field now recognizes that susceptibility is not simply a static product of genetics but that individuals may experience dynamic risk, skewed toward immune activation through therapeutic interventions and epigenetic modifications driven by ecological exposures. This review provides an updated overview of current and proposed genetic factors thought to predispose risk for severe T-cell-mediated DHRs
Modeling of graphene-based NEMS
The possibility of designing nanoelectromechanical systems (NEMS) based on
relative motion or vibrations of graphene layers is analyzed. Ab initio and
empirical calculations of the potential relief of interlayer interaction energy
in bilayer graphene are performed. A new potential based on the density
functional theory calculations with the dispersion correction is developed to
reliably reproduce the potential relief of interlayer interaction energy in
bilayer graphene. Telescopic oscillations and small relative vibrations of
graphene layers are investigated using molecular dynamics simulations. It is
shown that these vibrations are characterized with small Q-factor values. The
perspectives of nanoelectromechanical systems based on relative motion or
vibrations of graphene layers are discussed.Comment: 19 pages, 4 figure
Can Barrier to Relative Sliding of Carbon Nanotube Walls Be Measured?
Interwall interaction energies, as well as barriers to relative sliding of
the walls along the nanotube axis, are first calculated for pairs of both
armchair or both zigzag adjacent walls of carbon nanotubes with a wide range of
radiuses. It is found that for the pairs with the radius of the outer wall
greater than 5 nm both the interwall interaction energy and barriers to the
relative sliding per one atom of the outer wall only slightly depends on the
wall radius. A wide set of the measurable physical quantities determined by
these barriers are estimated as a function of the wall radius: shear strengths
and diffusion coefficients for relative sliding of the walls along the axis, as
well as frequencies of relative axial oscillations of the walls. For
nonreversible telescopic extension of the walls, maximum overlap of the walls
for which threshold static friction forces are greater than capillary forces is
estimated. Possibility of experimental verification of the calculated barriers
by measurements of the estimated physical quantities is discussed.Comment: 16 pages, 8 figure
Adjustment of the electric current in pulsar magnetospheres and origin of subpulse modulation
The subpulse modulation of pulsar radio emission goes to prove that the
plasma flow in the open field line tube breaks into isolated narrow streams. I
propose a model which attributes formation of streams to the process of the
electric current adjustment in the magnetosphere. A mismatch between the
magnetospheric current distribution and the current injected by the polar cap
accelerator gives rise to reverse plasma flows in the magnetosphere. The
reverse flow shields the electric field in the polar gap and thus shuts up the
plasma production process. I assume that a circulating system of streams is
formed such that the upward streams are produced in narrow gaps separated by
downward streams. The electric drift is small in this model because the
potential drop in narrow gaps is small. The gaps have to drift because by the
time a downward stream reaches the star surface and shields the electric field,
the corresponding gap has to shift. The transverse size of the streams is
determined by the condition that the potential drop in the gaps is sufficient
for the pair production. This yields the radius of the stream roughly 10% of
the polar cap radius, which makes it possible to fit in the observed
morphological features such as the "carousel" with 10-20 subbeams and the
system of the core - two nested cone beams.Comment: 8 pages, 1 figur
Mass Splitting and Production of and Measured in N Interactions
From a sample of decaying to the
final state, we have observed, in the hadroproduction experiment E791 at
Fermilab, and through
their decays to . The mass difference ) is measured to be ; for
, we find .
The rate of production from decays of the triplet is
(22\pm 2\pm 3) {%} of the total production assuming equal rate
of production from all three, as measured for and .
We do not observe a statistically significant baryon-antibaryon
production asymmetry. The and spectra of from
decays are observed to be similar to those for all 's
produced.Comment: 15 pages, uuencoded postscript 3 figures uuencoded, tar-compressed
fil
Large enhancement of deuteron polarization with frequency modulated microwaves
We report a large enhancement of 1.7 in deuteron polarization up to values of
0.6 due to frequency modulation of the polarizing microwaves in a two liters
polarized target using the method of dynamic nuclear polarization. This target
was used during a deep inelastic polarized muon-deuteron scattering experiment
at CERN. Measurements of the electron paramagnetic resonance absorption spectra
show that frequency modulation gives rise to additional microwave absorption in
the spectral wings. Although these results are not understood theoretically,
they may provide a useful testing ground for the deeper understanding of
dynamic nuclear polarization.Comment: 10 pages, including the figures coming in uuencoded compressed tar
files in poltar.uu, which also brings cernart.sty and crna12.sty files neede
Effects of demethylfruticuline A and fruticuline A from Salvia corrugata Vahl. on biofilm production in vitro by multiresistant strains of Staphylococcus aureus, Staphylococcus epidermidis and Enterococcus faecalis
Photoproduction of mesons associated with a leading neutron
The photoproduction of mesons associated with a leading
neutron has been observed with the ZEUS detector in collisions at HERA
using an integrated luminosity of 80 pb. The neutron carries a large
fraction, {}, of the incoming proton beam energy and is detected at
very small production angles, { mrad}, an indication of
peripheral scattering. The meson is centrally produced with
pseudorapidity {
GeV}, which is large compared to the average transverse momentum of the neutron
of 0.22 GeV. The ratio of neutron-tagged to inclusive production is
in the photon-proton
center-of-mass energy range { GeV}. The data suggest that the
presence of a hard scale enhances the fraction of events with a leading neutron
in the final state.Comment: 28 pages, 4 figures, 2 table
Measurement of the open-charm contribution to the diffractive proton structure function
Production of D*+/-(2010) mesons in diffractive deep inelastic scattering has
been measured with the ZEUS detector at HERA using an integrated luminosity of
82 pb^{-1}. Diffractive events were identified by the presence of a large
rapidity gap in the final state. Differential cross sections have been measured
in the kinematic region 1.5 < Q^2 < 200 GeV^2, 0.02 < y < 0.7, x_{IP} < 0.035,
beta 1.5 GeV and |\eta(D*+/-)| < 1.5. The measured cross
sections are compared to theoretical predictions. The results are presented in
terms of the open-charm contribution to the diffractive proton structure
function. The data demonstrate a strong sensitivity to the diffractive parton
densities.Comment: 35 pages, 11 figures, 6 table
Search for contact interactions, large extra dimensions and finite quark radius in ep collisions at HERA
A search for physics beyond the Standard Model has been performed with
high-Q^2 neutral current deep inelastic scattering events recorded with the
ZEUS detector at HERA. Two data sets, e^+ p \to e^+ X and e^- p \to e^- X, with
respective integrated luminosities of 112 pb^-1 and 16 pb^-1, were analyzed.
The data reach Q^2 values as high as 40000 GeV^2. No significant deviations
from Standard Model predictions were observed. Limits were derived on the
effective mass scale in eeqq contact interactions, the ratio of leptoquark mass
to the Yukawa coupling for heavy leptoquark models and the mass scale parameter
in models with large extra dimensions. The limit on the quark charge radius, in
the classical form factor approximation, is 0.85 10^-16 cm.Comment: 28 pages, 4 figures, accepted for publication in Physics Letters
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